The purpose of this study is to assess the efficacy and safety of trabectedin+DOXIL as a third-line chemotherapy regimen (treatment) in patients with platinum-sensitive advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer who received 2 previous lines of platinum-based chemotherapy.

A Randomized, Open-Label Study Comparing the Combination of YONDELIS and DOXIL/CAELYX With DOXIL/CAELYX Monotherapy for the Treatment of Advanced-Relapsed Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:

Overall survival [ Time Frame: Up to 2 months after the last participant has received the last dose of study medication or when 514 deaths have been observed, whichever is later ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression free survival [ Time Frame: Up to the date of disease progression or death measured up to 2 months after the last participant has received the last dose of study medication or when 514 deaths have been ] [ Designated as safety issue: No ]

Objective response rate [ Time Frame: Up to 2 months after the last participant has received the last dose of study medication or when 514 deaths have been observed, whichever is later ] [ Designated as safety issue: No ]

Area under the concentration curve of trabectedin as derived from sparse population pharmacokinetics [ Time Frame: Predose Day 1, 1 hour after start of study dose infusion, 10 minutes before the end of study dose infusion, and 0.5, 24, and 168 hours after the end of study dose infusion on Cycle 1 only ] [ Designated as safety issue: No ]

Minimum observed plasma concentration of trabectedin as derived from sparse population pharmacokinetics [ Time Frame: Predose Day 1, 1 hour after start of study dose infusion, 10 minutes before the end of study dose infusion, and 0.5, 24, and 168 hours after the end of study dose infusion on Cycle 1 only ] [ Designated as safety issue: No ]

Maximum observed plasma concentration of trabectedin as derived from sparse population pharmacokinetics [ Time Frame: Predose Day 1, 1 hour after start of study dose infusion, 10 minutes before the end of study dose infusion, and 0.5, 24, and 168 hours after the end of study dose infusion on Cycle 1 only ] [ Designated as safety issue: No ]

Number of participants affected by an adverse event [ Time Frame: Up to 30 days after the last participant has received the last dose of study medication ] [ Designated as safety issue: Yes ]

1.1 mg/m2 administered intravenously over 3 hours on Day 1 of each 21-day treatment cycle

Drug: DOXIL

30 mg/m2 administered intravenously over 90 minutes on Day 1 of each 21-day treatment cycle

Drug: Dexamethasone

20 mg administered intravenously on Day 1 of each 21-day treatment cycle approximately 30 minutes prior to study drug infusion

Active Comparator: Arm B: DOXIL

Drug: DOXIL

50 mg/m2 administered intravenously over 90 minutes on Day 1 of each 28-day treatment cycle

Detailed Description:

This is a randomized (individuals assigned to study treatment by chance), open-label (identity of assigned study drug will be known), active-controlled study in adult female patients with platinum-sensitive advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer who received 2 previous lines of platinum-based chemotherapy. Approximately 670 participants will be enrolled. Patients will be stratified by 4 criteria defined in the protocol and randomly assigned in a 1:1 ratio to the trabectedin+DOXIL combination therapy group (Arm A) or to the DOXIL (pegylated liposomal doxorubicin) monotherapy group (Arm B). During the treatment phase, patients will receive study drug infusions according to 21-day cycles in Arm A and 28-day cycles in Arm B. Treatment will continue until the occurrence of disease progression or unacceptable treatment toxicity, or until 2 cycles beyond a confirmed complete response is documented. Up to 2 additional cycles of study drug are allowed after complete response, at the discretion of the principal investigator. Efficacy assessments will be evaluated using Response Evaluation Criteria in Solid Tumors. Disease assessments, including assessments for patients who discontinue treatment for reasons other than disease progression, will be performed until disease progression, the start of subsequent anticancer therapy, withdrawal of consent, or the clinical cutoff date. Collection of survival status will continue until at least 514 deaths have been observed. Serial pharmacokinetic (PK) samples will be collected in a subset of patients who voluntarily consent to the PK portion of the study. Safety will be monitored throughout the study. An interim analysis of overall survival (OS) will be performed after approximately 308 participants have died. The final analysis of OS will occur when approximately 514 deaths have been observed.

Received first-line treatment with a platinum-based regimen and had no evidence of disease progression for >= 6 months after the last dose

Received second-line treatment with a platinum-based regimen, with progression of disease after attaining a complete response (CR) or partial response (PR)

Progression of disease based on imaging after the second-line platinum-based regimen (individuals treated with a pegylated liposomal doxorubicin-containing regimen as a second-line therapy are eligible if subsequent disease progression occurs >=9 months from the first dose)

Able to receive intravenous (IV) dexamethasone or an equivalent IV corticosteroid

Have a known BRCA 1/2 mutation status (for participants who do not have a known BRCA 1/2 status at screening, a blood sample will be collected to determine the status with the results available prior to randomization

Laboratory values within protocol -defined parameters

Have left ventricular ejection fraction by multigated acquisition scan (MUGA) scan or 2D-ECHO within normal limits for the institution

Have side effects (except alopecia) of prior treatment resolved to at least Grade 1 according to the National Cancer Institute - Common Terminology Criteria of Adverse Events (NCICTCAE) (Version 4.0)

Have a negative urine or serum pregnancy test at screening

Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

Diagnosis of ovarian carcinoma with mucinous histology

Had more than 2 prior lines of chemotherapy

Prior exposure to trabectedin or hypersensitivity to any of the excipients

History of another neoplastic disease (except non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin or cervical carcinoma in situ adequately treated) unless in remission for 5 years

Known allergies, hypersensitivity, or intolerance to Doxil, dexamethasone, or their excipients

Known history of central nervous system metastasis

Known significant chronic liver disease, such as cirrhosis or active hepatitis (potential participants who test positive for hepatitis B surface antigen or hepatitis C antibodies are allowed provided they do not have active disease requiring antiviral therapy)

Has any of the following medical conditions: uncontrolled diabetes, psychiatric disorder (including dementia) that prevents compliance with protocol, uncontrolled seizures, newly diagnosed deep vein thrombosis, active systemic infection that is likely to interfere with study procedure or results

Has any condition that, in the opinion of the investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01846611

Contacts

Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: